Minimum-energy conformations

Fig. 4.S Variation in torsional energy (AMBER force field) with O-C-C-0 torsion angle (to) for OCH -CHjO fragment. The minimum energy conformations arise for to = 60° and 300°.

The trans conformation corresponds to a torsion angle of 180°, the gauche(+) conformation to oni + 60° and the gauche -) conformation to -60°. These approximately correspond to the torsion anj of the three minimum energy conformations of butane. 

Fig. 9.19 Schematic illustration of an energy surface. A high-temperature molecular dynamics simulation may be ah to ooercome very high energy barriers and so explore conformational space. On minimisation, the appropriate minimum energy conformation is obtained (arrcrws).

Dmparison of various methods for searching conformational space has been performed cycloheptadecane (C17H34) [Saunders et al. 1990]. The methods compared were the ematic search, random search (both Cartesian and torsional), distance geometry and ecular dynamics. The number of unique minimum energy conformations found with 1 method within 3 kcal/mol of the global minimum after 30 days of computer processing e determined (the study was performed in 1990 on what would now be considered a / slow computer). The results are shown in Table 9.1. 

Due to the noncrystalline, nonequilibrium nature of polymers, a statistical mechanical description is rigorously most correct. Thus, simply hnding a minimum-energy conformation and computing properties is not generally suf-hcient. It is usually necessary to compute ensemble averages, even of molecular properties. The additional work needed on the part of both the researcher to set up the simulation and the computer to run the simulation must be considered. When possible, it is advisable to use group additivity or analytic estimation methods. 

Dithiolane (132) derivatives also possess non-planar skeletons the most important conformation is probably of symmetry C2 (half-chair). The dithiolane ring may be quite flexible and a minimum energy. conformation is only well defined if there is a bulky substituent at the 2-position. 

Fig. 6-4. Minimum energy conformations of L-PA and L-phenylalanine-A -methyl-anilide (L-PMA) based on molecular mechanics calculations and UV- and NMR-spectroscopic characterizations. (From Lepisto and Sellergren [25].)...

Figure 4.18 The structure of Tamiflu (oseltamivir phosphate), an antiviral agent active against type A influenza, and a molecular model of its minimum-energy conformation, as calculated by molecular mechanics.

Molecular mechanics (Chapter 4 Focus On) A computer-based method for calculating the minimum-energy conformation of a molecule. 

The minimum energy conformation yg if it exists in A should be the X-ray conformation Because the ground state is given by the X-ray conformation, the calculated free energy of all non-X-ray conformations should be higher than that of y - In other words ... 

Figure 3.4. Pentane. The diagram shows the four minimum-energy conformations of pentane. The global minimum is on the far left. Reflection and rotation of some of these geometries worrld generate more structures, but nothing with a different energy. Pentane is a simple molecule. More complicated molecules have many more conformations. Bryostatin 2 and PM-toxin A have so many mirrimtrm-energy conformations that to list them all would be a major undertaking and would require a large library to store the result.

According to molecular mechanics (MM) calculations, the minimum energy conformation of the enolate is a twist-boat (because the chair leads to an axial orientation of the f-butyl group). The enolate is convex in shape with the second ring shielding the bottom face of the enolate, so alkylation occurs from the top. 

In support of the alkylation studies, the putative minimum energy conformation of the l, 4-as and 1,4-trans diastereomers of 23 (R4 = Me, Pr1 R1 = Me, Bn, allyl R2 = Me, Bn) were calculated in a high-temperature molecular dynamic study using the Hyper-Chem 3 program and MM calculations. The higher stability of the m-diastereomers was confirmed by the calculations <1997JOC6424, 1998TA4275>. 

Roitberg, A. Elber, R., Modeling side chains in peptides and proteins application of the locally enhanced sampling technique and the simulated annealing methods to find minimum energy conformations, J. Chem. Phys. 1991, 95, 9277-9287... 

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